Mesangial cell hyperplasia is a feature common to several human glomerular diseases. The cause of this increased cell number is unknown. We assessed human mesangial cells in vitro and found that they possessed an insulin-like growth factor-I (IGF-I) receptor consisting of alpha and beta units (Mr 130k and 90k respectively). Fifty percent inhibition of IGF-I specific binding to the receptor required 1 x 10-9M IGF-I, greater than or equal to 1 x lO-6M insulin and 1 x 10-7M multiplication stimulating activity (MSA). Analysis of binding by the method of Scatchard revealed one type of IGF-I receptor with a kd = 1.35 x 10-9M, and a number per cell of 1.04 x 105. Binding studies on whole glomeruli was of similar specificity and there were 7.17 x 107 receptors per glomerulus (kd = 1.12 x 10-9M). Examination of the effect of IGF-I on the cell cycle revealed that cells treated with platelet derived growth factor (PDGF) had a rapid 3H-thymidine response which was abolished by anti-PDGF antibody. Similarly, the labeling index of cells pretreated with PDGF, washed and then exposed to IGF-I was increased, whereas if the order of ligand exposure was reversed, there was no such additive effect. Finally, PDGF increased RNA and protein synthesis, which was not enhanced by IGF-I. In summary, human mesangial cells, and whole glomeruli, possess IGF-I specific receptors and IGF-I was found to act as a progression factor in the cell cycle.